Potential of 2 Northern European brown seaweeds (Fucus serratus and Fucus vesiculosus) as enteric methane inhibitors in dairy cows.

The 2 brown seaweeds, Fucus serratus and Fucus vesiculosus, have demonstrated anti-methanogenic properties in vitro with reductions in CH4 production ranging from 53 to 63%. This study aimed to investigate the effects of the 2 Fucus seaweeds on enteric CH4 emissions, DMI, ECM, and nutrient digestibility when fed to dairy cows. The experiment was conducted using 4 multi-cannulated lactating Danish Holstein dairy cows, which over 3 experimental periods received either: 1) basal diet (CON; diet without any seaweed), 2) basal diet diluted with 4% (DM basis) Fucus serratus (SER), or 3) basal diet diluted with 4% (DM basis) Fucus vesiculosus (VES); resulting in one complete 3 × 3 Latin square and one incomplete 3 × 3 Latin square. Each period lasted 21 d and consisted of 14 d of adaptation, followed by 3 d of digesta sampling, and 4 d of gas exchange measurements using respiration chambers. Milk yield and feed intake were recorded daily. Blood samples were collected on d 15 and 17. All parameters were statistically analyzed using a mixed procedure of R. Opposite to what we had expected, neither of the 2 Fucus seaweeds reduced CH4 emissions from the dairy cows as daily CH4 production was significantly higher for both Fucus treatments compared with CON. Additionally, CH4 yield (g CH4/kg DMI) and intensity (g CH4/kg ECM) were significantly higher for SER compared with CON. Milk yield, DMI, and total-tract digestibility were unaffected by the treatments; however, SER resulted in lower milk protein yield (kg/d) and lower milk and blood plasma urea concentrations compared with CON. In conclusion, neither Fucus serratus (SER) nor Fucus vesiculosus (VES) showed potential as methane-mitigating feed additives when fed to dairy cows at an inclusion level of 4% of DM. The inclusion of the 2 brown seaweeds had no effects on DMI, milk yield, or total-tract digestibility.

Effects of dietary inclusion of 3 Nordic brown macroalgae on enteric methane emission and productivity of dairy cows.

Macroalgae are receiving increased attention as antimethanogenic feed additives for cattle, but most in vivo studies are limited to investigating effects of the red macroalgae Asparagopsis spp. Hence, this study aimed to investigate the CH4 mitigating potential of 3 brown macroalgae from the Northern Hemisphere when fed to dairy cows, and to study the effects on feed intake, milk production, feed digestibility, and animal health indicators. The experiment was conducted as a 4 × 4 Latin square design using 4 lactating rumen, duodenal, and ileal cannulated Danish Holstein dairy cows. The cows were fed a total mixed ration (TMR) without any macroalgae or the same TMR diluted with, on a dry matter basis, either 4% ensiled Saccharina latissima, 4% Ascophyllum nodosum (NOD), or 2% Sargassum muticum (MUT). Each period consisted of 14 d of adaptation, 3 d of digesta and blood sampling, and 4 d of gas exchange measurements using respiration chambers. Milk yield and dry matter intake (DMI) were recorded daily. Blood was sampled on d 13 and 16 and analyzed for health status indicators. None of the 3 species affected the CH4 emission. Moreover, milk yield and DMI were also unaffected. Total-tract digestibility of crude protein was significantly lower for NOD compared with other diets, and additionally, the NOD diet also tended to reduce total-tract digestibility of neutral detergent fiber compared with MUT. Blood biomarkers did not indicate negative effects of the dietary inclusion of macroalgae on cow health. In conclusion, none of the 3 brown macroalgae reduced CH4 emission and did not affect DMI and milk production of dairy cows, whereas negative effects on the digestibility of nutrients were observed when A. nodosum was added. None of the diets would be allowed to be fed in commercial dairy herds due to high contents of iodine, cadmium, and arsenic.

Short communication: Relationship between body condition score and plasma adipokines in early-lactating Holstein dairy cows.

We hypothesized that plasma adipokine concentrations of early-lactation dairy cows are related to body condition score (BCS) at calving and to markers of metabolic status of the cow. As part of a larger study with 117 multiparous Holstein dairy cows, which had high BCS (BCS >4.0) or normal BCS (3.25-3.5) at calving, 22 cows were randomly selected (n = 11 per group) to be enrolled in this study. Cows were divided into 2 groups based on their BCS at calving: (1) normal BCS with BCS of 3.35 ± 0.13 (mean ± SD) and (2) high BCS cows with BCS of 4.14 ± 0.17. The 22 selected animals did not have a clinically diagnosed health problem after calving. Blood samples were taken right after calving (d 1) and before morning feeding on d 8, 15, and 21 postpartum concurrently with body condition scoring for all cows. Blood samples were analyzed for plasma adiponectin, leptin, tumor necrosis factor-α, and IL-6. The mean BCS remained highest in high-BCS cows during the first 21 d in milk. Leptin concentrations decreased progressively for all cows after calving. However, differences in BCS at calving were not related to leptin concentrations. Adiponectin, IL-6, and tumor necrosis factor-α concentrations were neither influenced by days in milk nor BCS after calving. Leptin and the leptin-to-adiponectin ratio did not show any correlation at any time point during the first 21 d in milk with plasma concentrations of nonesterified fatty acids or ß-hydroxybutyrate, which are considered as markers of metabolic status. Only for IL-6 at d 8 did we find a strong correlation with metabolic status indicators. In conclusion, plasma adipokine concentrations during the first 3 wk postpartum were not related to BCS in lactating Holstein cows that were clinically healthy at calving.

Evaluation of the feeding value of Dichrostachys cinerea pods for fattening pigs in Cuba.

Dichrostachys cinerea (L.) Wight & Arn. is a tropical leguminous shrub widely regarded as an invasive species in Cuba, after having invaded a significant proportion of its arable land during the past decades. Concurrently, smallholder pig producers are highly constrained by the scarcity of protein feeds. This study aimed to assess the feeding value of D. cinerea pod meal (DCPM) as an alternative protein supplement for pigs in Cuban smallholder production systems. An on-farm feeding trial was carried out with three groups (N = 10) of growing-fattening pigs over 60 days, where DCPM replaced 0, 15, and 30% in DM of a dietary commercial concentrate. Then, in an in vivo digestibility trial with eight growing pigs, apparent digestibilities of DCPM were determined for dry matter (DM), organic matter (OM) and crude protein (CP). Finally, in vitro digestibilities for OM (fecal and ileal) and CP (ileal) were determined. In the feeding trial, pig body weight gains were not affected by increased dietary substitution levels of concentrate for DCPM. Blood parameters, with a few exceptions, did not show significant differences among groups. Values for in vivo OM and CP digestibilities were 40.81 and 50.26%, and substantially higher than in vitro values. In conclusion, our results showed that at least 30% of DM in commercial concentrate could be substituted by DCPM without affecting pig growth performances under Cuban smallholder conditions. The low digestibility of DCPM is, however, not acceptable for intensive pig production systems. In vitro enzyme digestibility methods developed for commercial pig feeds are not suitable for DCPM without further calibration.

Inhibition of local blood flow control systems in the mammary glands of lactating cows affects uptakes of energy metabolites from blood.

To test the effect of mammary blood flow on net uptakes of milk precursors by the mammary glands, inhibitors of nitric oxide synthase (NOS) and cyclooxygenase (COX) were infused into the mammary circulation of 4 lactating cows. Inhibitors were infused in a 4×4 Latin square design, where treatments were infusion for 1 h of saline, NOS inhibitor (Nω-nitro-l-arginine methyl ester hydrochloride), COX inhibitor (indomethacin), or both NOS + COX inhibitors into one external iliac artery. Para-aminohippuric acid was also infused to allow for estimation of iliac plasma flow (IPF), of which approximately 80% flows to the mammary glands. Blood samples were collected before, during, and after inhibitor infusion from the contralateral external iliac artery and ipsilateral mammary vein. Inhibition of COX and NOS each produced a decrease in IPF, although the NOS effect was smaller and IPF continued to be depressed throughout the recovery period. The combination of COX and NOS inhibition produced a 50% depression in IPF and there was no carryover into the recovery period. Treatments that depressed IPF also increased arterial concentrations of acetate, ß-hydroxybutyrate (BHBA), and glucose. Similarly, arteriovenous differences of acetate, BHBA, and glucose were all increased during IPF depression. To correct for a potential effect of arterial concentration, arteriovenous differences were normalized to arterial concentration, producing an extraction percentage. Inhibition of COX increased glucose extraction and tended to increase acetate and BHBA extraction. Dual inhibition only increased BHBA extraction and had no effect on mammary extraction of other metabolites. These extractions did not increase because clearances of glucose and TAG decreased as IPF decreased, and clearances of acetate and BHBA tended to decrease. Net uptake of TAG was depressed by dual NOS/COX inhibition, whereas uptakes of acetate, BHBA, and glucose were not affected by any of the treatments. To separate effects of flow from effects of arterial concentration, uptakes were regressed against IPF and arterial concentration simultaneously. According to the slopes of the regressions, a 10% decrease in IPF from the mean observed during saline infusion resulted in 3.8, 7.3, and 10.4% decreases in uptakes of acetate, glucose, and triacylglycerol, respectively. These findings indicate that mammary blood flow affects milk precursor uptake, and that clearance should not be assumed constant to predict mammary uptakes of milk precursors in situations where blood flow is changing.

Milk production response to varying protein supply is independent of forage digestibility in dairy cows.

The aim of this experiment was to examine whether the positive response in milk production to increased crude protein (CP) supply in dairy cows was dependent on the digestibility of the forage. Forty-eight lactating Danish Holstein cows were used in a 4 × 4 Latin square design experiment with 4 rations: (1) high digestibility and high CP concentration (HdHp), (2) high digestibility and low CP concentration (HdLp), (3) low digestibility and high CP concentration (LdHp), and (4) low digestibility and low CP concentration (LdLp). All rations contained 30% corn silage, 25% grass-clover silage, and 45% concentrate on a dry matter (DM) basis. Different digestibilities were obtained by replacing a high-digestible grass-clover silage combined with a high-digestible corn silage with a low-digestible grass-clover silage combined with a low-digestible corn silage. Organic matter digestibilities were 79.8 and 74.7% in the high- and low-digestibility rations, respectively. Dietary CP concentration in the ration was increased by substituting barley and sugar beet pulp with rapeseed meal and soybean meal, whereby CP increased from 13.9 to 14.0% (Lp) to 15.7 to 16.0% (Hp). All cows were offered 3 kg of the same concentrate per day in the automatic milking system in addition to the mixed ration. Every feeding period lasted 3 wk, and DM intake and milk yield were measured in the last week in each period, and milk samples for determining milk composition, including fatty acid content, and blood samples were taken during the last 3d of each period. Dry matter intake increased by 2.2 kg/d on Hd compared with Ld and by 0.7 kg/d on Hp compared with Lp. The positive effect on DM intake was reflected in the energy-corrected milk (ECM) yield, as a higher ration digestibility increased the ECM yield by 1.7 kg/d and a higher CP concentration increased it by 1.2 kg/d. We detected no interaction between forage digestibility and CP concentration on milk production. Reduced digestibility was accompanied by an increase in the plasma level of glucose, suggesting that other nutrients were limiting to milk production. In conclusion, milk production responses to dietary CP supply appeared independent of forage digestibility.

Late gestation undernutrition can predispose for visceral adiposity by altering fat distribution patterns and increasing the preference for a high-fat diet in early postnatal life.

We have developed a sheep model to facilitate studies of the fetal programming effects of mismatched perinatal and postnatal nutrition. During the last trimester of gestation, twenty-one twin-bearing ewes were fed a normal diet fulfilling norms for energy and protein (NORM) or 50% of a normal diet (LOW). From day 3 postpartum to 6 months (around puberty) of age, one twin lamb was fed a conventional (CONV) diet and the other a high-carbohydrate-high-fat (HCHF) diet, resulting in four groups of offspring: NORM-CONV; NORMHCHF; LOW-CONV; LOW-HCHF. At 6 months of age, half of the lambs (all males and three females) were slaughtered for further examination and the other half (females only) were transferred to a moderate sheep diet until slaughtered at 24 months of age (adulthood). Maternal undernutrition during late gestation reduced the birth weight of LOW offspring (P<0·05), and its long-term effects were increased adrenal size in male lambs and adult females (P<0·05), increased neonatal appetite for fat-(P=0·004) rather than carbohydrate-rich feeds (P<0·001) and reduced deposition of subcutaneous fat in both sexes (P<0·05). Furthermore, LOW-HCHF female lambs had markedly higher visceral:subcutaneous fat ratios compared with the other groups (P<0·001). Postnatal overfeeding (HCHF) resulted in obesity (.30% fat in soft tissue) and widespread ectopic lipid deposition. In conclusion, our sheep model revealed strong pre- and postnatal impacts on growth, food preferences and fat deposition patterns. The present findings support a role for subcutaneous adipose tissue in the development of visceral adiposity, which in humans is known to precede the development of the metabolic syndrome in human adults.

Effect of fumaric acid in combination with Asparagopsis taxiformis or nitrate on in vitro gas production, pH, and redox potential.

Reduction in enteric methane (CH4) emissions from cattle can be achieved through use of feed additives, which often results in increased emission of hydrogen (H2). The objective of this study was to investigate in vitro effects of a known hydrogen sink, fumaric acid, in combination with either of 2 methane inhibitors, the macroalga Asparagopsis taxiformis or nitrate, on CH4 and H2 production, feed degradability, pH, and redox potential. A corn silage (0.5 g; control) was incubated in buffered rumen fluid with the addition of 0.025 g of nitrate (Nit), 0.025 g of dried A. taxiformis (Asp), 0.025 g of nitrate + 0.025 g of fumaric acid (Nit+Fum), or 0.025 g of dried A. taxiformis + 0.025 g of fumaric acid (Asp+Fum). Accumulated gas production was determined using the AnkomRF system equipped with airtight gasbags. There were 9 replicates per treatment with 3 replicates per treatment stopped after 24, 36, and 48 h of incubation. The amount of undegraded feed was determined by filtration. Gas composition was determined by gas chromatography. Degradable dry matter, degradable organic matter, pH, redox potential, and gas production data were analyzed using a mixed model. Asp and Asp+Fum reduced CH4 production by 98% or greater at all incubation times, whereas Nit and Nit+Fum reduced CH4 production (mL of CH4/g of dry matter) by 52% to 63% compared with the control. Hydrogen was only detectable in gas from Asp and Asp+Fum treatments, with no difference in H2 production between the 2 treatments. The treatments had only minor effects on redox potential in the fermented rumen fluid, and pH was lowest for treatments including A. taxiformis. In conclusion, both A. taxiformis and nitrate reduced CH4 production. Fumaric acid in combination with A. taxiformis did not reduce H2 production, and treatments including nitrate did not result in any detectable levels of H2. Future dose-response in vitro studies will contribute to investigating the potential of fumaric acid as a hydrogen sink during CH4 mitigation.

EPA guidance on treatment of negative symptoms in schizophrenia.

Negative symptoms of schizophrenia remain a major therapeutic challenge. The progress in the conceptualization and assessment is not yet fully reflected by treatment research. Nevertheless, there is a growing evidence base regarding the effects of biological and psychosocial interventions on negative symptoms. The importance of the distinction between primary and secondary negative symptoms for treatment selection might seem evident, but the currently available evidence remains limited. Good clinical practice is recommended for the treatment of secondary negative symptoms. Antipsychotic treatment should be optimized to avoid secondary negative symptoms due to side effects and due to positive symptoms. For most available interventions, further evidence is needed to formulate sound recommendations for primary, persistent, or predominant negative symptoms.However, based on currently available evidence recommendations for the treatment of undifferentiated negative symptoms (including both primary and secondary negative symptoms) are provided. Although it has proven difficult to formulate an evidence-based recommendation for the choice of an antipsychotic, a switch to a second-generation antipsychotic should be considered for patients who are treated with a first-generation antipsychotic. Antidepressant add-on to antipsychotic treatment is an option. Social skills training is recommended as well as cognitive remediation for patients who also show cognitive impairment. Exercise interventions also have shown promise. Finally, access to treatment and to psychosocial rehabilitation should be ensured for patients with negative symptoms. Overall, there is definitive progress in the field, but further research is clearly needed to develop specific treatments for negative symptoms.

EPA guidance on assessment of negative symptoms in schizophrenia.

BACKGROUND: During the last decades, a renewed interest for negative symptoms (NS) was brought about by the increased awareness that they interfere severely with real-life functioning, particularly when they are primary and persistent. METHODS: In this guidance paper, we provide a systematic review of the evidence and elaborate several recommendations for the conceptualization and assessment of NS in clinical trials and practice. RESULTS: Expert consensus and systematic reviews have provided guidance for the optimal assessment of primary and persistent negative symptoms; second-generation rating scales, which provide a better assessment of the experiential domains, are available; however, NS are still poorly assessed both in research and clinical settings.This European Psychiatric Association (EPA) guidance recommends the use of persistent negative symptoms (PNS) construct in the context of clinical trials and highlights the need for further efforts to make the definition of PNS consistent across studies in order to exclude as much as possible secondary negative symptoms. We also encourage clinicians to use second-generation scales, at least to complement first-generation ones.The EPA guidance further recommends the evidence-based exclusion of several items included in first-generation scales from any NS summary or factor score to improve NS measurement in research and clinical settings. Self-rated instruments are suggested to further complement observer-rated scales in NS assessment.Several recommendations are provided for the identification of secondary negative symptoms in clinical settings. CONCLUSIONS: The dissemination of this guidance paper may promote the development of national guidelines on negative symptom assessment and ultimately improve the care of people with schizophrenia.

Continuous lactation effects on mammary remodeling during late gestation and lactation in dairy goats.

The present study aimed to 1) elucidate whether continuous milking during late gestation in dairy goats negatively affects mammary remodeling and hence milk production in the subsequent lactation, and 2) identify the regulatory factors responsible for changes in cell turnover and angiogenesis in the continuously lactating mammary gland. Nine multiparous dairy goats were used. One udder half was dried off approximately 9 wk prepartum (normal lactation; NL), and the other udder half of the same goat was milked continuously (continuous lactation; CL) until parturition or until the half-udder milk yields had dropped to below 50 g/d. Mammary biopsies were obtained from each udder half just before the NL gland was dried off (before dry period), within the first 2 wk after drying-off (early dry period, samples available only for NL glands), in the mid dry period, within the last 2 wk before parturition (late dry period), and at d 1 (the day of parturition), 3, 10, 60, and 180 of lactation. Mammary morphology was characterized in biopsies by quantitative histology, and cell turnover was determined by immunohistochemistry (terminal deoxynucleotidyl transferase dUTP nick end labeling and Ki-67). Transcription of genes encoding factors involved in mammary epithelial cell (MEC) turnover and vascular function was quantified by quantitative reverse transcription PCR. Results demonstrated that omitting the dry period was possible in goats but was not as easy as claimed before. Renewal of MEC was suppressed in CL glands, which resulted in a smaller MEC population in the subsequent lactation. At the time of parturition (and throughout lactation), the mammary glands subjected to CL had smaller alveoli, more fully differentiated MEC, and a substantially larger capillary fraction compared with NL glands. The continuously lactating gland thus resembled a normally lactating gland in an advanced stage of lactation. None of the studied genomic factors could account for these treatment differences. The described characteristics in CL glands compared with NL glands indicated a gland maintained in lactation for a longer period.

Mammary remodeling in primiparous and multiparous dairy goats during lactation.

Milk production is generally lower but lactation persistency higher in primiparous (PP) than in multiparous (MP) goats. This may be related to differences in development and maintenance of mammary gland function, but the underlying mechanisms are not well understood. The present study aimed to elucidate whether differences in lactational performance between PP and MP mammary glands are related to the time course of development and maintenance, not only of the mammary epithelial cell (MEC) population, but also of the mammary vasculature that sustains synthetic activity. Mammary biopsies were obtained from both mammary glands of 3 PP and 6 MP (>or=2 parity) dairy goats at parturition (d 1), d 10, 60, and 180 of lactation. Gene transcription relating to MEC turnover and vascular function was quantified by real-time reverse transcription-PCR, mammary morphology was characterized (quantitative histology), and cell turnover was determined (terminal deoxynucleotidyl transferase dUTP nick end labeling assay and Ki-67). Primiparous glands showed higher expression for the genes involved in angiogenesis; namely, vascular endothelial growth factor receptor 2, and angiopoietin 1 and 2 and their receptor, a few days after parturition (d 10). Primiparous glands also had higher rates of MEC proliferation in early lactation. It therefore appears that initiation of lactation is associated with development and growth of the mammary gland into early lactation, which continues for a longer period in PP compared with MP glands. In addition, MEC survival was found to be higher in PP glands throughout lactation, and MEC in PP glands underwent more extensive differentiation. This could explain the reported flatter lactation curve and higher lactation persistency in PP glands. Although some of the genes included in this study were differentially expressed in PP and MP glands during the course of lactation, it was not possible to identify any specific genomic factor(s) that could account for the differences between PP and MP glands with respect to mammary development and MEC survival during lactation. It remains to be established why parity number affects MEC and vascular development and survival during lactation, and, in particular, which regulatory mechanisms are involved.

Short-term safety of preoperative administration of botulinum toxin A for the treatment of large ventral hernia with loss of domain.

PURPOSE: Preoperative intramuscular-administered botulinum toxin A (BTA) in the lateral abdominal muscles prior to abdominal wall reconstruction has been reported to produce a flaccid paralysis and improve the primary closure rate of large ventral hernias with loss of domain. Complications to this treatment remain sparsely described. The aim of the current study was to report safety and short-term outcome of abdominal wall reconstruction aided by BTA administration. METHODS: This was a retrospective two-center study including all patients undergoing abdominal wall reconstruction for ventral hernia aided by preoperative BTA administration to the lateral abdominal muscles. Data were retrieved from patient charts and included preoperative demographic and perioperative information as well as postoperative 30-day complications and readmissions. RESULTS: A total of 37 patients underwent BTA administration prior to hernia repair. The mean age and body mass index were 59.5 (SD 10.1) years and 31.1 (SD 5.2) kg/m2. The BTA injections were administered mean 31.6 days (SD 10.0) prior to the hernia repair. One (2.7%) patient reported pain as a complication immediately after the BTA administration. Subsequent to the hernia repair, six (16.2%) patients were readmitted within 30 days. Nine patients (24.3%) had wound complications and medical complications occurred in seven (18.9%) patients. CONCLUSIONS: We found early preoperative administration of BTA a safe adjunct to large ventral hernia repair, without adverse events related to the administration preoperative. Future studies should further highlight the efficacy of preoperative BTA for reconstruction of otherwise untreatable hernias.

Effects of alternative feed additives to medicinal zinc oxide on productivity, diarrhoea incidence and gut development in weaned piglets.

The use of medicinal zinc oxide (ZnO) must be phased out by 2022, thus prompting an urgent need for alternative strategies to prevent diarrhoea in weaner piglets. The objectives of this study were to assess the impact on weaner piglet performance, diarrhoea incidence and gut development, when (1) dietary ZnO supplementation was substituted by alternative commercial products based on macroalgae, specific probiotics or synbiotics, or (2) dietary ZnO inclusion was reduced from 2500 to 1500 ppm. A total of 4680 DLY piglets (DanBred, Herlev, Denmark), weaned around 35 days of age, were randomly assigned according to sex and BW to six different dietary treatment groups. A basal diet was supplemented with no ZnO (NC = negative control), 2500 ppm ZnO (PC = positive control), 1500 ppm ZnO (RDZ = reduced dose of ZnO) or commercial macroalgae (OceanFeed™ Swine = OFS), probiotic Miya-Gold or synbiotic GærPlus products. The piglets entered and exited the weaner unit at ~7.0 and 30 kg BW, respectively. In-feed ZnO was provided the first 10 days post-weaning, while the alternative supplements were fed throughout the weaner period. As expected, the average daily feed intake, average daily weight gain (ADG), feed conversion ratio (FCR) and diarrhoea incidence were improved in the PC compared to NC group (P < 0.05) during phase 1 consistent with improved indices of villi development observed in subgroups of piglets sacrificed 11 days post-weaning. Reduction of ZnO to 1500 ppm lowered ADG (P < 0.05) and slightly increased incidence of diarrhoea during the first 10 days after weaning (but not later) without affecting FCR. None of the three alternative dietary additives, including a 10-fold increased dose of GærPlus than recommended, improved piglet performance, gut health and gut development above that of NC piglets. The OFS piglets sacrificed 11 days after weaning had significantly lower weights of hindgut tissue and contents compared to the PC group, consistent with antimicrobial activity of the product, which was detected from anaerobic in vitro fermentation. In conclusion, dietary ZnO supplementation during the first 10 days post-weaning may be reduced from 2500 to 1500 ppm without major negative implications for weaner piglet performance and health in herds under a high management level. However, none of the alternative dietary supplements were able to improve piglet performance or gut health, when ZnO was omitted from the diet.

Glucose homeostasis and metabolic adaptation in the pregnant and lactating sheep are affected by the level of nutrition previously provided during her late fetal life.

This study investigated whether undernutrition (UN) during late fetal life can programme the subsequent adult life adaptation of glucose homeostasis and metabolism during pregnancy and lactation. Twenty-four primiparous experimental ewes were used. Twelve had been exposed to a prenatal NORM level of nutrition (maternal diet approximately 15 MJME/d) and 12 to a LOW level of nutrition (maternal diet approximately 7 MJME/d) during the last 6 weeks pre-partum. The experimental ewes were subjected to two intravenous glucose tolerance tests (IGTT) in late gestation (one prior to (G-IGTT) and one by the end of a feed restriction period (RG-IGTT)), and a third around peak lactation (L-IGTT). LOW had lower basal insulin concentrations during lactation, and significantly decreased absolute insulin secretion during the L-IGTT in spite of similar glucose tolerance, indicating increased insulin sensitivity in LOW during lactation. There was no effect of prenatal UN on glucose tolerance during G-IGTT, however, during RG-IGTT LOW was more glucose intolerant and apparently more insulin resistant compared to NORM. In conclusion, UN during late fetal life in sheep impairs subsequent pancreatic insulin secretory capacity during adult life, and reduces plasticity of down-regulation of insulin secretion in response to a metabolic challenge. Furthermore, prenatal UN appears to programme mechanisms, which in young adult females can shift the insulin hypersensitivity observed during early lactation into an insulin resistance observed during late gestation and feed restriction. Early postnatal UN caused by lowered milk intake in early postnatal life may have contributed to these phenomena.

Continuous lactation in dairy cows: effect on milk production and mammary nutrient supply and extraction.

Reports over the past decade have indicated that normal lactational performance can be achieved in genetically superior and high-producing dairy cows, even when the dry period between 2 lactations is omitted. The hypothesis tested in this experiment was that normal lactogenesis I and metabolic function may be achievable in continuously milked high-yielding dairy cows as a result of the genetic selection for lactation performance and hence longevity of mammary epithelial cells. The milk production and mammary nutrient uptake in response to omission of the dry period for cows with an expected peak milk yield higher than 45 kg/d were studied in 28 Holstein dairy cows managed without bovine somatotropin. Performance and metabolic parameters were followed in late gestation and in the following early lactation. Fourteen cows were milked continuously throughout late gestation, and another 14 dairy cows experienced a 7-wk prepartum dry period. Continuous milking during the prepartum period reduced milk production in the following early lactation period by >20%. The reduced milk production could not be readily ascribed to inefficiency of the mechanisms responsible for nutrient uptake by the lactating mammary epithelial cells, nor to systemic endocrine changes. This suggests that lowered mammary nutrient uptake must have been associated with reduced mammary blood flow, metabolic activity, or both, most likely as a result of disturbed lactogenesis I prepartum or lactogenesis II postpartum triggered by as yet unknown local mechanisms. Milk protein content was elevated by 0.4 percentage units in the continuously milked cows. The underlying reason is unknown, but given the current pricing system for milk, it deserves to be further investigated.

The histamine H1 receptor is not involved in local control of mammary blood flow in dairy cows.

Low concentrations of the essential amino acid histidine in circulation have been shown to increase mammary blood flow and it has been suggested that this effect is mediated by histamine. The hypotheses tested in this experiment were that interstitial histamine concentrations in the mammary gland are related to arterial His concentrations and that mammary blood flow is reduced by extracellular histamine via H(1) receptors. The hypotheses were tested by infusing saline or chlorpheniramine, a blocker of the H(1) histamine receptor, into the arterial supply of the mammary glands of lactating cows infused with 44 g/h of amino acid mixtures with or without His for 10 h. Infusates were administered in a 2 x 2 factorial arrangement within a 4 x 4 Latin square to 4 multiparous Holstein cows in mid lactation. Exclusion of His from the infusate decreased protein content in milk from the infused udder half from 3.98 to 3.77%, and increased arterial alpha-aminonitrogen concentration from 3.2 to 3.4 mM. Neither the decreased arterial His concentration nor the H(1) blocker affected plasma flow to the infused udder half. We conclude that histamine is not involved in the regulation of mammary blood flow. The H(1) blocker decreased milk production in the infused udder half from 4.6 to 3.5 kg without affecting protein, fat, and lactose percentages, suggesting an inhibition of milk ejection. Cows on chlorpheniramine ate less feed during the infusion than saline-infused cows, which resulted in lower arterial concentrations and mammary uptakes of acetate. The efficiency of plasma triacylglycerol uptake across the mammary glands was decreased by chlorpheniramine but net uptake of long-chain fatty acids was not affected. The mechanism by which an amino acid deficiency influences mammary blood flow does not involve histamine signaling through the H(1) receptor and remains unidentified.

Fetal over- and undernutrition differentially program thyroid axis adaptability in adult sheep.

OBJECTIVE: We aimed to test, whether fetal under- or overnutrition differentially program the thyroid axis with lasting effects on energy metabolism, and if early-life postnatal overnutrition modulates implications of prenatal programming. DESIGN: Twin-pregnant sheep (n = 36) were either adequately (NORM), under- (LOW; 50% of NORM) or overnourished (HIGH; 150% of energy and 110% of protein requirements) in the last-trimester of gestation. From 3 days-of-age to 6 months-of-age, twin lambs received a conventional (CONV) or an obesogenic, high-carbohydrate high-fat (HCHF) diet. Subgroups were slaughtered at 6-months-of-age. Remaining lambs were fed a low-fat diet until 2½ years-of-age (adulthood). METHODS: Serum hormone levels were determined at 6 months- and 2½ years-of-age. At 2½ years-of-age, feed intake capacity (intake over 4-h following 72-h fasting) was determined, and an intravenous thyroxine tolerance test (iTTT) was performed, including measurements of heart rate, rectal temperature and energy expenditure (EE). RESULTS: In the iTTT, the LOW and nutritionally mismatched NORM:HCHF and HIGH:CONV sheep increased serum T3, T3:T4 and T3:TSH less than NORM:CONV, whereas TSH was decreased less in HIGH, NORM:HCHF and LOW:HCHF. Early postnatal exposure to the HCHF diet decreased basal adult EE in NORM and HIGH, but not LOW, and increased adult feed intake capacity in NORM and LOW, but not HIGH.Conclusions: The iTTT revealed a differential programming of central and peripheral HPT axis function in response to late fetal malnutrition and an early postnatal obesogenic diet, with long-term implications for adult HPT axis adaptability and associated consequences for adiposity risk.

Differential hypothalamic leptin sensitivity in obese rat offspring exposed to maternal and postnatal intake of chocolate and soft drink.

BACKGROUND/OBJECTIVE: Intake of high-energy foods and maternal nutrient overload increases the risk of metabolic diseases in the progeny such as obesity and diabetes. We hypothesized that maternal and postnatal intake of chocolate and soft drink will affect leptin sensitivity and hypothalamic astrocyte morphology in adult rat offspring. METHODS: Pregnant Sprague-Dawley rats were fed ad libitum chow diet only (C) or with chocolate and high sucrose soft drink supplement (S). At birth, litter size was adjusted into 10 male offspring per mother. After weaning, offspring from both dietary groups were assigned to either S or C diet, giving four groups until the end of the experiment at 26 weeks of age. RESULTS: As expected, adult offspring fed the S diet post weaning became obese (body weight: P<0.01, %body fat per kg: P<0.001) and this was due to the reduced energy expenditure (P<0.05) and hypothalamic astrogliosis (P<0.001) irrespective of maternal diet. Interesting, offspring born to S-diet-fed mothers and fed the S diet throughout postnatal life became obese despite lower energy intake than controls (P<0.05). These SS offspring showed increased feed efficiency (P<0.001) and reduced fasting pSTAT3 activity (P<0.05) in arcuate nucleus (ARC) compared with other groups. The findings indicated that the combination of the maternal and postnatal S-diet exposure induced persistent changes in leptin signalling, hence affecting energy balance. Thus, appetite regulation was more sensitive to the effect of leptin than energy expenditure, suggesting differential programming of leptin sensitivity in ARC in SS offspring. Effects of the maternal S diet were normalized when offspring were fed a chow diet after weaning. CONCLUSIONS: Maternal intake of chocolate and soft drink had long-term consequences for the metabolic phenotype in the offspring if they continued on the S diet in postnatal life. These offspring displayed obesity despite lowered energy intake associated with alterations in hypothalamic leptin signalling.

Two subgroups of antipsychotic-naive, first-episode schizophrenia patients identified with a Gaussian mixture model on cognition and electrophysiology.

Deficits in information processing and cognition are among the most robust findings in schizophrenia patients. Previous efforts to translate group-level deficits into clinically relevant and individualized information have, however, been non-successful, which is possibly explained by biologically different disease subgroups. We applied machine learning algorithms on measures of electrophysiology and cognition to identify potential subgroups of schizophrenia. Next, we explored subgroup differences regarding treatment response. Sixty-six antipsychotic-naive first-episode schizophrenia patients and sixty-five healthy controls underwent extensive electrophysiological and neurocognitive test batteries. Patients were assessed on the Positive and Negative Syndrome Scale (PANSS) before and after 6 weeks of monotherapy with the relatively selective D2 receptor antagonist, amisulpride (280.3±159 mg per day). A reduced principal component space based on 19 electrophysiological variables and 26 cognitive variables was used as input for a Gaussian mixture model to identify subgroups of patients. With support vector machines, we explored the relation between PANSS subscores and the identified subgroups. We identified two statistically distinct subgroups of patients. We found no significant baseline psychopathological differences between these subgroups, but the effect of treatment in the groups was predicted with an accuracy of 74.3% (P=0.003). In conclusion, electrophysiology and cognition data may be used to classify subgroups of schizophrenia patients. The two distinct subgroups, which we identified, were psychopathologically inseparable before treatment, yet their response to dopaminergic blockade was predicted with significant accuracy. This proof of principle encourages further endeavors to apply data-driven, multivariate and multimodal models to facilitate progress from symptom-based psychiatry toward individualized treatment regimens.